Now playing catch-up to bluebird, Vertex and CRISPR send in their pitch for blood disorder cell therapy
If all things go according to plan, the FDA could start reviewing the first-ever filing for a CRISPR therapy this November.
Vertex and CRISPR Therapeutics say they have wrapped up their lengthy talks with the agency and gotten regulators on board for a rolling review beginning later this year — with the submission package due to be complete in the first quarter of 2023.
While the partners once hoped that they would be the first to bring a once-and-done therapy to the US market for sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT), bluebird bio beat them to the punch with the recent FDA approval of Zynteglo. The filing also marks a slight delay to earlier plans of filing in late 2022, although it wasn’t entirely unexpected.
As then-SVB Securities analyst Rick Bienkowski noted in June, the last patient dosed in the study that formed the basis of Vertex and CRISPR’s pitch “will not have reached the 12-month follow-up timepoint until January 2023.” If the FDA requires that every patient make it over that line, he wrote, then BLA filings would need to be pushed to early 2023 — which ended up being the case.
Although the companies didn’t specify the reason, they did previously mention that the FDA was looking for an entire year of follow-up.
The partners added, however, that they’re on track to file for approval in the EU and UK by the end of 2022.
CTX001, now dubbed exagamglogene autotemcel or exa-cel, was born out of a partnership between Vertex and CRISPR that began in 2015. In a major sign of confidence, Vertex paid CRISPR $900 million cash two years ago to take an additional 10% of future sales from the therapy, which is an autologous cell therapy featuring ex vivo gene edits done with CRISPR/Cas9 technology.
Specifically, a patient’s own hematopoietic stem cells are edited to produce high levels of fetal hemoglobin. The concept is similar to bluebird’s Zynteglo, except that Zynteglo contains the hemoglobin subunit beta gene and the edits are delivered with a lentiviral vector.
At their last update, Vertex and CRISPR reported that of 44 patients with TDT who received exa-cel, 42 had stopped red blood cell transfusions. As for the sickle cell disease trial, all 31 patients have had no severe vaso-occlusive crises.
It remains to be seen whether safety concerns related to the conditioning agent patients need to receive before getting exa-cel would cause problems in the review.